This invention relates to a solid-phase binding assay system for measuring analytes.
Many solid-phase immunoassays involve surface illumination and consequent light emissions from molecules attached to the surface. Generally, these emissions travel in all directions. Either these divergent emissions must be collected with expensive and awkward light collection optics to achieve high sensitivity or the inherent inefficiencies and consequent low signal to noise ratio must be accepted.
Many immunoassay systems have been developed using different physically measurable properties of reagents to provide a measurement of an analyte concentration. Radio immunoassay (RIA), immunofluorescence, chemiluminescence, enzyme immunoassays (EIA), free radical immunoassays (FRAT), light scattering nephelometry, transistor bridge probes, indium reflective surfaces, and ultrasonic probes have been applied. These systems use the highly selective reaction between a primary binding reagent material such as an antibody or antigen and an analyte selectively binding therewith.
An attempt by others to develop an optical probe comprising a metal covered diffraction grating coated with a monoclonal antibody specific for a virus, bacterium or other desired antigen has been described by Moffatt, A. Genetic Engineering News, p. 18, October 1986. The shift in wavelength of reflected light is apparently determined and correlated to a concentration in analyte.
A reflectance method for quantification of immunological reactions on polished crystalline silicon wafer surfaces has been described by Arwin, H. et al, Analytical Biochemistry, 154:106-112 (1985). Indium surface reflection methods are described by Giaver in U.S. Pat. Nos. 3,853,467, 3,926,564, 3,960,488, 3,960,489, 3,960,490, 3,975,238, 3,979,184, 3,979,509, 4,011,308, 4,018,886, 4,054,646, 4,115,535, 4,172,827 and 4,181,501. Liquid layer thicknesses can be monitored by a reflectance method described in U.S. Pat. No. 3,960,451.
Biosensors such as field effect transistors probes and their use in assays are described by Pace, S., Medical Instrumentation, (19(4):168-172 (1985). Polysilicon surfaces are included among the possible biosensor surfaces to which primary binding reagents can be attached.
Other patents of interest include U.S. Pat. Nos. 4,537,861; 4,558,012; 4,647,544; 4,820,649; 4,876,208; 4,886,761; 5,089,387; 5,120,131; 5,196,350; and RE 33,581.
The most sensitive instrument for the measurement of optical phase shift due to physical displacement or refractive index change or both is the optical interferometer. There are many different interferometer designs. Measurements made with interferometers include: 1) the attempt to detect gravitational radiation (A. Abramovici, et al. "LIGO: The Laser Interferometer Gravitational-Wave Observatory" Science 256, Apr. 17, 1992, p. 325), 2) positioning of the cutting head and work piece in precision machining (C. Evans, "Precision Engineering: an Evolutionary View", Cranfield Press 1989), 3) tectonic plate movement in geology for earthquake prediction (P. L. Bender, "Laser Measurement of Long Distances", Proc. IEEE, Vol. 55, No. 6, June 1967, PP. 1039-1045) and 4) microarcsecond astrometry (R. D. Reasenberg, et al. "Microarcsecond Optical Astrometry: An Instrument and its Astrophysical Applications", The Astronomical Journal, 96 (5) 1988).